The continuing goal of this work is to clarify the initiation and development of the lipid-rich core region of the atherosclerotic fibrous plaque, as discerned primarily in human aorta and coronary arteries from autopsy cases. Studies performed in Years 01-02 have shown (1) consistent core development in small, distinct raised lesions, termed "fibrolipid lesions" and regarded as fibrous plaque progenitors, (2) an absence of macrophage-like cells in the core, by routine electron microscopy, and early disappearance of elastin from the core, and (3) by ultrastructural lipid staining and quantitative localization, the predominance of elastin as a site for early lipid deposition in aortic intima. Based in part on these results, the following general hypothesis is proposed: Extracellular interactions between lipoproteins and connective tissue elements, especially elastin, play a central role in early core formation, although the metabolic activities of macrophages and smooth muscle cells modulate the process considerably. The aims of the proposed studies are - (1) To determine the relationship of specifically determined constituents - including cholesterol, cholesteryl ester, and apoprotein B - to core region basophilia (light microscopy) and granular matrix (electron microscopy), (2) to determine the presence and location of certain cell types - macrophage, mature smooth muscle, secretory smooth muscle - identified immunologically and by other means, in and near the developing core region, (3) to confirm, by immunocytochemical and other methods, the extent of elastin participation in perifibrous lipid deposition and the impression of elastin disappearance from the core region, and (4) to determine the form in which lipoprotein lipid binds to elastin in vitro, the nature of the binding, and the reversibility and other characteristics of the process. Together these studies will contribute substantially toward proving and elucidating the stated hypothesis. The importance of the core region of the fibrous plaque is underscored by its role in causing plaque rupture or ulceration, leading to acute thrombotic or thromboembolic events.